TENKASI

Posology 1 200 mg administered as a single dose by intravenous infusion over 1 hours. 2). Renal impairment No dose adjustment is needed in patients with mild or moderate renal impairment. Very limited data are available in patients with severe renal impairment.

2), however caution should be exercised when prescribing oritavancin in patients with severe renal impairment. Oritavancin is not removed from blood by haemodialysis procedures. Hydroxypropyl-β-cyclodextrin (HPβCD) is almost exclusively eliminated through the kidneys via glomerular filtration; its pharmacokinetics in patients with severe renal impairment has not been evaluated.

2). The pharmacokinetics of oritavancin in patients with severe hepatic impairment (Child-Pugh Class C) has not been evaluated, however based on pharmacokinetic parameters, severe hepatic impairment is not expected to have an impact on oritavancin exposure.

Therefore, no dose adjustment is required, even if caution should be exercised when prescribing oritavancin to patients with severe hepatic impairment (Child-Pugh Class C). Paediatric population The safety and efficacy of oritavancin in children and adolescents (<18 years) have not yet been established.

No data are available. Method of administration Intravenous use. There are two oritavancin medicinal products (Tenkasi 1 200 mg and Tenkasi 400 mg) that: • Are supplied in different dose strengths of oritavancin. • Have different recommended duration of infusion.

• Have different preparation instructions, including differences in reconstitution, dilution, and compatible diluents. 6). The single 1 200 mg vial should first be reconstituted with 40 mL of sterile water for injections (WFI). 6). Refer to Tenkasi 400 mg for relevant information on the other oritavancin medicinal product.

Summary of the safety profile The most commonly reported adverse reactions (≥5%) were: nausea, hypersensitivity reactions, infusion site reactions, and headache. 1%). 3%). Female patients had a higher reporting rate for adverse reactions than male patients.

Tabulated list of adverse reactions Adverse reactions for oritavancin from the pooled Phase 3 ABSSSI clinical trials with single dose oritavancin are listed by system organ class in the following table. Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1//1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 4) ** Infusion site reactions includes: infusion site phlebitis, infusion site erythema, extravasation, induration, pruritus, rash, oedema peripheral.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme.

uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Hypersensitivity reactions Serious hypersensitivity reactions, including anaphylactic reactions and anaphylactic shock have been reported with the use of oritavancin. If an acute hypersensitivity reaction occurs during oritavancin infusion, oritavancin should be discontinued immediately and appropriate supportive care should be instituted.

No data are available on cross-reactivity between oritavancin and other glycopeptides, including vancomycin. g. vancomycin, telavancin). Due to the possibility of cross-hypersensitivity, there should be careful monitoring of patients with any history of glycopeptide hypersensitivity during and after the infusion.

Infusion related reactions Oritavancin is given via intravenous infusion over 1 hour to minimise the risk of infusion related reactions. Intravenous infusions of oritavancin can cause reactions such as flushing of the upper body, urticaria, pruritus and/or rash.

Infusion-associated reactions characterised by chest pain, chest discomfort, chills, tremor, back pain, neck pain, dyspnoea, hypoxia, abdominal pain and fever have been observed with the use of oritavancin, including after the administration of more than one dose of oritavancin during a single course of therapy.

8). Renal impairment The solubiliser HPβCD is excreted in urine. Clearance of HPβCD may be reduced in patients with renal impairment. The clinical significance of this finding is unknown. 1). In mixed infections where Gram-negative and/or certain types of anaerobic bacteria are suspected, oritavancin should be co-administered with appropriate antibacterial agent(s).

Concomitant use of warfarin Oritavancin has been shown to artificially prolong prothrombin time (PT) and international normalised ratio (INR) for up to 12 hours, making the monitoring of the anticoagulation effect of warfarin unreliable up to 12 hours after an oritavancin dose.

5). Oritavancin concentrations that are found in the blood of patients following administration of a single dose have been shown to artificially prolong: • aPTT for up to 120 hours, • PT and INR for up to 12 hours, • Activated Clotting Time (ACT) for up to 24 hours, • Silica Clot Time (SCT) for up to 18 hours, and • Dilute Russell’s Viper Venom Test (DRVVT) for up to 72 hours.

These effects result from oritavancin binding to and preventing the action of the phospholipid reagents which activate coagulation in commonly used laboratory coagulation tests. For patients who require aPTT monitoring within 120 hours of oritavancin dosing, a non-phospholipid dependent coagulation test such as a Factor Xa (chromogenic) assay or an alternative anticoagulant not requiring aPTT monitoring may be considered.

The Chromogenic Factor Xa Assay, the Thrombin Time (TT) assay and the assays used for the diagnosis of Heparin Induced Thrombocytopenia (HIT) are not affected by oritavancin. 6 μg/mL did not affect an assay for activated protein C resistance (APCR), suggesting that there is a low likelihood that oritavancin will interfere with this test.

However, APCR is a phospholipid-based test and it cannot be ruled out that higher concentrations of oritavancin that may occur during clinical use could interfere with this test. No effect of oritavancin on the in vivo coagulation system was observed in nonclinical and clinical studies.

Clostridioides difficile-associated diarrhoea Antibacterial-associated colitis and pseudomembranous colitis have been reported for oritavancin and may range in severity from mild to life threatening diarrhoea. 8). In such a circumstance, the use of supportive measures together with the administration of specific treatment for Clostridioides difficile should be considered.

Superinfection The use of antibacterial medicinal products may increase the risk of overgrowth of non-susceptible micro-organisms. If superinfection occurs, appropriate measures should be taken. 8). Patients should be monitored for signs and symptoms of osteomyelitis after administration of oritavancin.

If osteomyelitis is suspected or diagnosed, appropriate alternative antibacterial therapy should be instituted. 8). If newly emergent abscesses occur, appropriate measures should be taken. Limitations of the clinical data In the two major trials in ABSSSI the types of infections treated were confined to cellulitis, abscesses and wound infections only.

Other types of infections have not been studied. There is limited experience in clinical studies in patients with bacteraemia, peripheral vascular disease or neutropenia, in immunocompromised patients, in patients aged > 65 years, in patients with severe renal impairment and in infections due to Streptococcus pyogenes.

6 mg/ml.

1. 5).